Non-invasive prenatal testing (NIPT) can identify six fetal red blood cell (RBC) antigens for which the antibodies are associated with fetal anemia and by extension, hemolytic disease of the fetus and newborn (HDFN), which is recognized as being the most common cause of fetal anemia worldwide.
What is HDFN?
Hemolytic disease of the fetus and newborn (HDFN) is an immune-mediated red blood cell disorder that occurs when a baby’s RBCs break down quickly, which is called hemolysis. HDFN is caused by a mismatch between a mother’s and her baby’s blood type (A, B, AB, or O) or Rhesus (Rh) factor (Rh-positive or Rh-negative) during pregnancy.
A systematic search on the topic was conducted in four databases up until May 2024. Findings from the analysis were presented by Faezah Aghajani, MD, and colleagues at the Society for Maternal-Fetal Medicine (SMFM) 2025 Pregnancy Meeting, which was held between Jan. 27 and Feb. 1, in Aurora, CO.
The researchers sought to evaluate the diagnostic accuracy of NIPT for the identification of fetal RBC antigen genotypes. Their search comprised studies that had implemented NIPT for the detection of fetal RBC antigens in pregnancies at risk for alloimmunization and thus for potential HDFN.
Sensitivity, specificity, area under the curve and diagnostic odds ratios were computed. The analysis was performed based on laboratory technique, which included polymerase chain reaction and next-generation sequencing.
Read more about the prognosis of HDFN
Subgroup analyses were performed based on the following six fetal antigens:
- RhC
- Rhc
- RhD
- RhE
- Kell
- Duffy (Fya)
Overall, there were 52 studies included in the analysis, among which 48 (37,228 maternal samples) utilized polymerase chain reaction and four (170 maternal samples) utilized next-generation sequencing.
Regarding the diagnostic accuracy of the 6 antigens using polymerase chain reaction assays, the pooled sensitivity varied between 98% and 100%. Additionally, the pooled specificity using the polymerase chain reaction technique ranged between 99% and 100%.
Regarding the diagnostic accuracy of the six antigens with use of the next-generation sequencing technique, the pooled sensitivity was 100% for all of the antigens, and the pooled specificity was 100% for the 6 antigens as well.
The authors concluded, “Clinical adoption of NIPT for the detection of fetal anemia for both alloimmunized and RhD-negative non-alloimmunized pregnant individuals may streamline care[,] and reduce unnecessary treatment monitoring…and patient anxiety.”
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